Peña Fernando, Aguileta Miguel-Angel
Departamento de Farmacobiología, Cinvestav-Sede Sur, Calz. de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
Neurosci Lett. 2007 Mar 30;415(3):288-93. doi: 10.1016/j.neulet.2007.01.032. Epub 2007 Jan 19.
The pre-Bötzinger complex (PBC), part of the ventral respiratory group that is responsible for inspiratory rhythm generation, contains at least two types of pacemaker neurons. In vitro studies have shown that bursting properties of one type of pacemaker relies on a riluzole-sensitive persistent sodium current, whereas bursting of a second type is sensitive to flufenamic acid (FFA), a calcium-dependent nonspecific cationic current blocker. In vitro, under control conditions, the PBC generates fictive eupneic activity that depends on both riluzole-sensitive and FFA-sensitive pacemaker neurons. During hypoxia the PBC generates fictive gasping activity and only riluzole-sensitive pacemaker neurons appear to be necessary for this rhythm. We carried out pharmacological experiments to test the role of respiratory pacemaker neurons in vivo by performing plethysmographic recordings on neonate mice. As reported in vitro, eupnea activity in vivo is abolished only if both FFA and riluzole are coadministered intracisternally, but not when either of them is administered independently. On the other hand riluzole, but not FFA, drastically reduced gasping generation and compromised the ability of mice to autoresucitate. Neither substance P nor forskolin was able to reestablish respiratory activity after riluzole and FFA coapplication. Our results confirm in vitro reports and suggest that eupnea generation in neonates requires a complex neuronal network that includes riluzole- and FFA-sensitive elements and that gasping activity depends mostly on a riluzole-sensitive mechanism.
前包钦格复合体（PBC）是腹侧呼吸组的一部分，负责吸气节律的产生，包含至少两种类型的起搏神经元。体外研究表明，一种起搏神经元的爆发特性依赖于一种对利鲁唑敏感的持续性钠电流，而另一种的爆发对氟芬那酸（FFA）敏感，FFA是一种钙依赖性非特异性阳离子电流阻滞剂。在体外，在对照条件下，PBC产生依赖于利鲁唑敏感和FFA敏感起搏神经元的虚拟平静呼吸活动。在缺氧期间，PBC产生虚拟喘息活动，并且只有对利鲁唑敏感的起搏神经元似乎对这种节律是必需的。我们进行了药理学实验，通过对新生小鼠进行体积描记记录来测试呼吸起搏神经元在体内的作用。如体外报道的那样，只有当FFA和利鲁唑都经脑池内共同给药时，体内的平静呼吸活动才会被消除，而单独给予它们中的任何一种时则不会。另一方面，利鲁唑而非FFA，显著减少了喘息的产生并损害了小鼠的自动复苏能力。在利鲁唑和FFA共同应用后，P物质和福斯高林都无法重建呼吸活动。我们的结果证实了体外报道，并表明新生儿平静呼吸的产生需要一个复杂的神经元网络，其中包括对利鲁唑和FFA敏感的元件，并且喘息活动主要依赖于一种对利鲁唑敏感的机制。
